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G-四链体与神经诱导剂的联合作用作为人类胶质母细胞瘤治疗的替代方法。

A Combined Effect of G-Quadruplex and Neuro-Inducers as an Alternative Approach to Human Glioblastoma Therapy.

作者信息

Pavlova Galina, Kolesnikova Varvara, Samoylenkova Nadezhda, Drozd Sergey, Revishchin Alexander, Shamadykova Dzhirgala, Usachev Dmitry Y, Kopylov Alexey

机构信息

Laboratory of Neurogenetics and Genetics Development, Institute of Higher Nervous Activity and Neurophysiology of Russian Academy of Sciences (RAS), Moscow, Russia.

Federal State Autonomous Institution «N. N. Burdenko National Medical Research Center of Neurosurgery» of the Ministry of Health of the Russian Federation, Moscow, Russia.

出版信息

Front Oncol. 2022 Apr 28;12:880740. doi: 10.3389/fonc.2022.880740. eCollection 2022.

Abstract

Cancer cell reprogramming based on treatment with G-quadruplex, having antiproliferative power, along with small molecules able to develop iPSCs into neurons, could create a novel approach to diminish the chance of glioblastoma recurrence and circumvent tumor resistance to conventional therapy. In this research, we have tested several combinations of factors to affect both total cell cultures, derived from tumor tissue of patients after surgical resection and two subfractions of this cell culture after dividing them into CD133-enriched and CD133-depleted populations (assuming CD133 to be a marker of glioblastoma stem-like cells). CD133 and CD133 cells exhibit different responses to the same combinations of factors; CD133 cells have stem-like properties and are more resistant. Therefore, the ability to affect CD133 cells provides a possibility to circumvent resistance to conventional therapy and to build a promising strategy for translation to improve the treatment of patients with glioblastoma.

摘要

基于具有抗增殖能力的G-四链体处理以及能够将诱导多能干细胞诱导分化为神经元的小分子进行癌细胞重编程,可能会创造一种新方法来降低胶质母细胞瘤复发的几率,并规避肿瘤对传统疗法的耐药性。在本研究中,我们测试了多种因素组合对两种细胞培养物的影响,一种是手术切除后取自患者肿瘤组织的全细胞培养物,另一种是将该细胞培养物分为富含CD133和缺乏CD133的群体(假设CD133为胶质母细胞瘤干细胞样细胞的标志物)后的两个亚组分。CD133⁺和CD133⁻细胞对相同的因素组合表现出不同的反应;CD133⁺细胞具有干细胞样特性且更具抗性。因此,影响CD133⁺细胞的能力为规避对传统疗法的耐药性以及构建一种有望转化为改善胶质母细胞瘤患者治疗效果的策略提供了可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/acf6/9109612/37b81c662495/fonc-12-880740-g001.jpg

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